Structure of Hemagglutinin Fusion Peptide and Correlation of the Structure with Fusion Catalysis
Enveloped viruses, like influenza virus are coated with a lipid membrane, and fusion peptides present in the lipid envelope are responsible for the fusion between the viral and the host cell membrane on infection. The fusion peptide is highly conserved such that modest mutation can arrest membrane fusion. Despite the fusion peptide’s critical role in fusion, there is no clear consensus in the literature of the structure and function of the influenza fusion peptide. Research over the last 25 years on the influenza fusion peptide showed very different structures; 20-residue influenza fusion peptide adopts open boomerang structure while the 23-residue adopts a tightly packed closed helical hairpin structure in detergents.1,2 Based on the different interhelical geometries different membrane-binding mechanisms were proposed. The different functional models were based on different structures in detergents, but influenza fusion peptide induces fusion of membranes and not detergents, so the membrane structures are more relevant for function. We recently showed that both the 20- and 23-residue influenza fusion peptide adopts similar structures in membrane.3 In this talk, we will discuss about the determination of the structure of influenza fusion peptide in membranes. Later, how the structural features were correlated to the function of the influenza fusion peptide will be discussed.
1. Han, X.; Bushweller, J. H.; Cafiso, D. S.; Tamm, L. K. Nat. Struct Biol. 2001, 8, 715
2. Lorieau, J. L.; Louis, J. M.; Bax, A. Proc. Natl. Acad. Sci. U.S.A. 2010, 107, 11341
3. Ghosh, U.; Xie, L.; Jia, L.; Liang, S.; Weliky, D.P. J Am. Chem. Soc. 2015, 137, 7548